Evaluation of Surrogate Markers for Insulin Resistance for Defining Metabolic Syndrome in Urban Indian Adolescents.

Objective: To compare parameters of insulin resistance, with special reference to McAuley index, in urban Indian adolescents, and to establish their cut-off values for defining metabolic syndrome. Design: Cross-sectional study. Setting: Schools located in four different geographical zones of Delhi, India. Participants: 695 apparently healthy adolescents grouped as normal weight (298), overweight (205) and obese (192). Outcome measures: Cut-off point for indices of insulin resistance was assessed by fasting insulin, insulin glucose ratio, and other methods (HOMA model, QUICKI, McAuley index) to define metabolic syndrome. Results: The McAuley index increased progressively from normal weight to obese adolescents in both sexes. McAuley index was significantly lower in adolescents with metabolic syndrome (5.36 ± 1.28 vs. 7.05 ± 1.88; P<0.001). McAuley index had the highest area under curve of receiver operator characteristics [0.82 (0.02)] as compared to other indices of insulin resistance. McAuley index of 6.23 had the highest specificity (88%) with sensitivity of 63.3% for diagnosing metabolic syndrome, whereas insulin glucose ratio had the highest sensitivity (79.7%) but low (55.5%) specificity. McAuley index was negatively correlated with height (r= -0.257, P=<0.001), weight (r= -0.537, P=<0.001), body mass index (r= -0.579, P<0.001), waist circumference (r= -0.542, p<0.001), and waist hip ratio (r= -0.268, P<0.001). Conclusions: Among various parameters of insulin resistance, McAuley index had the highest specificity, and insulin glucose ratio had the highest sensitivity in diagnosing metabolic syndrome in urban Indian adolescents.

Performance of Accredited Social Health Activists to Provide Home-based Newborn Care: A Situational Analysis.

Objective: To assess Accredited social health activists’ (ASHAs) ability to recognize illness in infants aged less than 2 months. Methods: Investigators observed 25 ASHAs conducting 47 visits. Results: ASHA-investigator agreement on the need to further assess infants was intermediate (kappa 0.48, P<0.001). Using IMNCI’s color codes, ASHAs misclassified 80% of infants. ASHAs did not follow home-based newborn care formats and skipped critical signs. Overall ASHA-investigator agreement on diagnosis was poor (kappa=0.23, P=0.01). Conclusion: There is a need for improved training, tools, and supportive supervision.

T-lineage acute lymphoblastic leukemia and parvovirus infection in a child with neurofibromastosis-1.

Neurofibromatosis (NF-1) patients have an increased risk of developing malignancies most commonly rhabdomyosarcomas, optic gliomas, brain tumors and non-lymphocytic leukemias. Acute lymphoblastic leukemia (ALL) has been infrequently reported in association with NF-1. We describe a rare association of NF-1, T-lineage ALL and parvovirus infection in a 12-year-old child. In addition, it is also to emphasize that a high index of suspicion should be kept for parvovirus B19 infection as a cause of bicytopenia/pancytopenia in ALL patients following induction chemotherapy.

Percentage Body Fat in Apparently Healthy School Children From Northern India.

Context: Increased prevalence of obesity in childhood and adolescence, defined by the use of body mass index (BMI), has drawn attention towards direct measurement of body fat Objective: To develop age-and sex-specific reference distribution of body fat in apparently healthy North-Indian children in the age group of 7-17 years and to assess agreement between obesity (defined by BMI) and excess body fat Design: Study subjects for this cross sectional study included1640 apparently healthy school children (825 boys; 815 girls) aged 7-17 years. Total body fat was measured by dual energy X-rays absorptiometry (DXA). The excess body fat by DXA was defined by two methods, prevalence matching and with the use of 85th and 95th centile cutoffs. Results: The mean ± SD, 3rd, 10th, 25th, 50th, 75th, 90th and 97th centile values of percentage body fat (PBF) are presented. PBF was highly correlated with BMI in both boys and girls (all boys: r=0.76, P<0.0001; all girls r=0.81, P<0.0001). There was no significant difference noted in PBF between boys and girls at the age of 7-8 years. From 9 years onwards, girls had significantly higher PBF than boys. Moderate degree of agreement was observed between BMI and PBF by DXA by both methods. Conclusions: Smoothened reference distribution of PBF for North-Indian children and adolescents in Delhi are provided. Indian children accumulate more body fat during peri-pubertal years in comparison with US children.

Interleukin-5, interleukin-6, interleukin-8 and tumour necrosis factor-alpha levels obtained within 24-h of admission do not predict high-risk infection in children with febrile neutropenia.

Purpose: Biomarkers that can predict the severity of febrile neutropenia (FN) are potential tools for clinical practice. Objective: The objective of this study is to evaluate the reliability of plasma interleukin (IL) levels as indicators of high-risk FN. Materials and Methods: Children with haematological malignancies and FN were enrolled prospectively. A blood sample was obtained within 24-h of admission for estimation of IL-5, IL-6, IL-8 and tumour necrosis factor-alpha (TNF-α) level by the enzyme-linked immunosorbent assay. Patients were stratified into three groups. Group I (low-risk): No focus of infection; Group II: Clinical/radiological focus of infection; Group III: Microbiologically proven infection or FN related mortality. Groups II and III were analysed as high-risk. The cytokines were assessed at three different cut-off levels. Results: A total of 52 episodes of FN in 48 patients were evaluated. The mean age was 6 years (range: 2-13). Primary diagnosis included acute lymphoblastic leukaemia (82%), non-Hodgkin's lymphoma (13%) and acute myeloid leukaemia (5%). Absolute neutrophil count was < 200 cells/μl in half and 200-500 in 23%. Majority were categorised as Group I (69%), followed by Group II (16%) and III (15%). The range of IL-5 was too narrow and similar in the two risk-groups to be of any relevance. The best sensitivity of TNF-α and IL-6 for high-risk group was 78% and 70%, respectively. The highest specificity observed was 35%. The negative predictive value of IL-6, IL-8 and TNF-α exceeded 80%. Conclusion: IL-5, IL-6, IL-8 and TNF-α failed as predictors of clinically localised or microbiologically documented infection in children with chemotherapy induced FN. However, IL-6, IL-8 and TNF-α could be useful in excluding the possibility of high-risk infection.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Serodiagnosis of celiac disease in children referred for evaluation of anemia: A pediatric hematology unit's experience.

Background: Children presenting with typical clinical features of celiac disease (CD) are diagnosed relatively easily, however, diagnosis remains challenging and is often delayed when they present with 'difficult to treat anemia' without overt gastrointestinal manifestations. Index study was undertaken to report profile of patients referred to pediatric hematology unit with 'difficult anemia' who subsequently were diagnosed with CD. Materials and Methods: The records of 83 patients (1988-2008) with CD were scrutinized retrospectively who had presented with predominant hematological manifestations. Results: CD was confirmed histologically in 31 (37%), while 52 (63%) were diagnosed by serology alone. The mean age at diagnosis was 8.0 ± 2.8 years. The mean duration of symptom-diagnosis interval was 40.9 ± 30.6 months. Eighty-one (98%) children had anemia (Hb < 11 g/dl) and 55 (66%) had received iron supplements without discernible benefit. Thirty-nine (47%) patients received a blood transfusion. Thirty-six (43%) patients did not have diarrhea. Majority of the patients had either a microcytic-hypochromic (48%) or dimorphic (43%) anemia. Twenty-four (33%) had thrombocytosis, while 5 (7%) had thrombocytopenia. Mean duration of follow-up for patients on roll in the clinic for more than six months was 17.7 ± 20.9 months. Conclusion: Pediatricians and hematologists need to be aware of the extra-intestinal manifestations of CD. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in children presenting with predominantly hematological manifestations. Investigations for CD are recommended in children presenting with iron deficiency anemia refractory to hematinics or who have coexisting growth retardation. Necessity for biopsy in overtly symptomatic cases is discussed.

Overt testicular disease at diagnosis in childhood acute lymphoblastic leukemia: Prognostic significance and role of testicular irradiation.

Objective. To analyze the prognostic impact of overt testicular disease (OTD) at diagnosis and role of testicular irradiation in the same. Methods. Data of 579 boys treated at our center over 16 years was reviewed. Results. Fourteen (2.4%) males had OTD. 10 (71.4%) of these had high-risk disease. Patients with OTD, had a significantly higher incidence of mediastinal-adenopathy (p=0.001), hyperleucocytosis (p=0.004) and CNS disease at presentation (p<0.0001) compared to patients in continuous complete remission (CCR). 4 of the 11 patients with OTD, who opted for therapy, had relapse; 2 are in CCR. Although, survival in patients with OTD was inferior (p=0.183) compared to patients without OTD, it was not an independent prognostic factor (p=0.47). In the entire study cohort, symptom-diagnosis interval (p=0.006), white cell (p=0.001) and platelet count (p=0.001) at presentation were significantly associated with survival (Cox multivariate regression analysis). Conclusions. OTD was not an independent prognostic factor, despite association with high-risk features. Survival outcome was inferior. The observations indicate the need of revaluation of the present protocol with incorporation of intermediate dose and subsequently high-dose methotrexate (after assessment for toxicity and tolerance), risk-stratified therapy and plausibly omission of testicular irradiation.

Hypovitaminosis D and Hypocalcemic Seizures in Infancy.

Background: Hypocalcemia accounts for a majority of seizures in infants reporting to the emergency ward of our hospital. Objective: To evaluate the role of Vitamin D deficiency in the etiology of hypocalcemic seizures in infancy. Design and Setting: Cross sectional hospital based study, from April 2006-March 2007. Subjects: 60 infants with hypocalcemic seizures and their mothers (study group) and 60 healthy breastfed infants with their lactating mothers (control group). Measurements: Vitamin D [25(OH) D] and intact parathormone levels. Results: High prevalence of hypovitaminosis D [25(OH)D levels <10 ng/mL] was observed in study mothers (85%), control mothers (50%), study infants (90%), and control infants (41.7%). Mean serum 25(OH) D values in study mothers and their infants (6.54 ± 5.32 ng/mL and 4.92 ± 4.62 ng/mL) were significantly lower than those of motherinfant pairs (9.06 ± 4.78 ng/mL and 9.03 ± 4.63 ng/mL) in the control group (P<0.001). A strong positive correlation of 25(OH) D levels between mothers and their infants was seen in both the study and control populations (P<0.001). Of the 54 study infants who had 25(OH)D levels <10ng/ mL, 48 (89%) were born to mothers who also had 25(OH) D levels <10ng/mL. Conclusions: Vitamin D deficiency is a major cause of hypocalcemic seizures in infants. Infants born to vitamin D deficient mothers are at a significantly higher risk to develop hypocalcemic seizures.

Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons.

Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL). Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(e)s. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04). Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

Iodine Nutrition in Upper Socioeconomic School Children of Delhi.

We assessed the iodine nutrition of upper socioeconomic strata school children from Delhi to identify its association with goiter, thyroid autoimmunity or thyroid function. After informed consent of parents, all assenting students (n=997) from one randomly selected section of each class from five private schools representing all the zones of Delhi) were evaluated for goiter, urinary iodine excretion, thyroid function and antibody status. Median urinary iodine was 35.28μg/dL. Goiter was present in 123 (12.3%) and positive anti-TPO antibodies in 17 (2.6%). Increased urinary iodine was associated with thyroid dysfunction, though not with goiter.

High incidence of Epstein Barr virus infection in childhood acute lymphocytic lukemia: A preliminary study.

Introduction: Epstein Barr virus (EBV) has a unique association with several human malignancies, especially lymphoproliferative disorders, mainly lymphomas in adults. There is paucity of data pertaining to EBV association with various cancers in India . Objective : The study aims to investigate the association of EBV in childhood leukemia. Material and Methods: Patients attending pediatric oncology services of the referral center have been included in the study. Twenty-five consecutive pediatric patients with acute lymphocytic lukemia (ALL) were subjected to EBV studies employing sensitive polymerase chain reaction followed by hybridization for presence of Bam H1-W region of EBV genome and detection of anti Z EBV replication activator (ZEBRA) antibodies using Western blot. Positive control included a case of Burkitt's lymphoma and infectious mononucleosis each. Raji cells were used as positive control with each test. Results: The PCR for EBV was positive in 8/25 patients of ALL. Western blot test using anti ZEBRA antibodies was positive in 5/25(20%) cases of ALL. Considering PCR as the gold standard, 32% of the children with ALL had evidence of active EBV replication. The positive controls were consistently positive. None of the 30 healthy laboratory controls, 22 age matched disease controls, 12 cases of AML and 15 cases of multiple myeloma were positive either by PCR or Western blots assays (P < 0. 01). There was no statistically significant correlation between duration of therapy and EBV positivity (P > 0.05). Conclusion: These studies indicate that a significant number of patients with ALL show evidence of active EBV replication.

Fulminant candida infection in an infant with acrodermatitis enteropathica.

Acrodermatitis Enteropathica (AE) is an important nutritional disorder of children affecting both innate and cell mediated immunity. It predisposes to secondary bacterial and candida superinfections. We describe an infant with typical features of AE who had candida infection with a fulminant course. Need of early recognition and prompt initiation of therapy for fungal infection in AE is emphasized.

Langerhans' cell histiocytosis: experience from a single center.

Clinical profile, disease-distribution and outcome of Langerhans cell histiocytosis (LCH) is presented in this retrospective analysis. There were 69 children with LCH from January 1986 to December 2004. Diagnosis was presumptive in the majority. The age ranged from 2 months to 12 years. Multisystem disease was documented in 48 (69.6%) children. Evidence of hepatic dysfunction was detected in 25 (36.2%). An elevated serum alkaline phosphatase was a prominent observation in patients with hepatic involvement. Children with localized disease received oral steroids, while cases with disseminated/multi-system disease were treated with prednisolone and, vinblastine or etoposide. 20 (54%) children with disseminated disease and organ dysfunction died. A favorable outcome was documented in all but one case with localized disease. Portal hypertension developed in 3 cases, all of whom had a fatal outcome. Twelve (17.4%) patients had diabetes insipidus. Disseminated disease with organ dysfunction was observed to be a predictor of fatal outcome.

Distal arthrogryposis syndrome.

A 5-month-old male infant presented with weak cry, decreased body movements, tightness of whole body since birth, and one episode of generalized seizure on day 4 of life. He was born at term by elective caesarian section performed for breech presentation. The child had failure to thrive, contractures at elbow and knee joints, hypertonia, microcephaly, small mouth, retrognathia, and camptodactyly. There was global developmental delay. Abdominal examination revealed umbilical and bilateral inguinal hernia. Visual evoked response and brainstem evoked response audiometry were abnormal. Nerve conduction velocity was normal. Magnetic resonance imaging of brain revealed paucity of white matter in bilateral cerebral hemispheres with cerebellar and brain stem atrophy. The differential diagnoses considered in the index patient were distal arthrogryposis (DA) syndrome, cerebroculofacioskeletal syndrome, and Pena Shokier syndrome. The index patient most likely represents a variant of DA: Sheldon Hall syndrome.

Evaluation of the role of ultrasonography in diagnosis of autoimmune thyroiditis in goitrous children.

OBJECTIVES: To evaluate the role of thyroid ultrasound in children with autoimmune thyroiditis diagnosed either on cytopathology or by the presence of thyroid peroxidase antibodies. DESIGN AND SETTINGS: Children presenting for the first time to the Thyroid Clinic at the Institute of Nuclear Medicine and Allied Sciences for the complaint of goiter over a two year period (January 2005-December 2006) were studied. SUBJECTS: 695 school children (244 boys and 451 girls) aged 5-18 year were studied. METHODS: Children were subjected to thyroid ultrasound, cytopathology, thyroid peroxidase antibody and thyroid function tests. RESULTS: Overall, 16% of goitrous children had hypoechogenicity on ultrasound, 15.2% had cytopathological evidence of thyroiditis, 10.6% had positive thyroid peroxidase antibodies and 25.2% had abnormal thyroid function tests. Subjects with hypoechogenicity had higher percentage of thyroiditis on cytopathology (41.4% vs. 10.3%; P<0.01), thyroid peroxidase antibody positivity (30.6% vs. 6.8%; P<0.01) and thyroid dysfunction (46.8% vs. 21.2%; P<0.01) than those with normal echogenicity. CONCLUSION: Thyroid USG has a useful, though limited, role in excluding thyroid disease in children. The sensitivity of echogenicity for the diagnosis of autoimmune thyroiditis in children is less than that reported in adults.

Ultrasound evaluation of thyroid size: a large nationwide study of schoolchildren in India.

BACKGROUND: Ultrasound assessment of thyroid volume is considered a more objective method than clinical palpation for the diagnosis of goitre. We used ultrasonography to establish normal reference cut-off points of thyroid volume in schoolchildren of different socioecomonic groups in India and compared the results with international norms. METHODS: In a cross-sectional study, we clinically examined 27,250 children from the lower and higher socioeconomic strata (SES) from all over India to determine their goitre staging. A single sonologist, using ultrasonography, assessed the thyroid volume in a subset of 15,986 children (8463 from the lower and 7523 from the higher SES). Students were recruited from at least one school each representing the higher and the lower SES, from cities located in 5 zones of India. Children with known thyroid disorders were excluded from the study. RESULTS: Clinical evaluation revealed a mean goitre prevalence of 19.9% (23.2% in girls; 16.5% in boys; 17.1% in the higher SES; 23.5% in the lower SES). The thyroid volume as assessed by ultrasonography was significantly higher in children from the lower SES (mean 5.65 ml, SE 0.02) compared with those from the higher SES (mean 5.02 ml, SE 0.02) after adjusting for the imbalance in body surface area (p < 0.001). Using international norms (WHO 2004), the prevalence of goitre in various body surface area categories among children who had no goitre on clinical examination ranged from 48.2% to 75.1% for boys and 23.2% to 67.4% for girls. CONCLUSION: The striking discrepancy in the prevalence of goitre assessed by using clinical examination and ultrasound techniques suggests that the norms recommended by WHO based on ultrasound techniques are not appropriate for India.